The hypothesis is proposed that prostaglandin biosynthesis by breast cancers is stimulated by prolactin in tumors which are hormonally sensitive. This is based on evidence that prolactin stimulates prostaglandin production in normal murine mammary tissue and on preliminary data suggesting that prostaglandin levels are higher in estrogen receptor positive human breast cancers. This hypothesis predicts the following experimental observation: (1) prostaglandin concentrations should be higher in hormonally sensitive tumors; (2) prolactin should stimulate prostaglandin production in hormonally sensitive tumors; (3) estrogens should induce prostaglandin synthetase in hormonally sensitive breast tumors; or (4) estrogens should increase the sensitivity of the prostaglandin synthetase system to prolactin in hormonally sensitive tumors. We plan to test these predictions using radioimmunoassay measurement of tissue prostaglandin E2, prostaglandin synthetase and biologically available enzyme substrate in human breast tumors which are classified as hormonally sensitive by the presence of estrogen receptors and in the hormonally dependent rat mammary tumors, MTW9 and MTW9A which have been exposed to altered (elevated and/or lowered) levels of estrogens and prolactin. These latter manipulations will be accomplished by injection of estrogen, ovariectomy and implantation and excision of the prolactin secreting tumor MtTW10.